Antidepressant effect of geranylgeranylacetone in a chronic mild stress model of depression and its possible mechanism.

Depression is a highly debilitating and widely distributed illness in the general population. Geranylgeranylacetone (GGA), a non-toxic anti-ulcer drug, has been reported to have protective effects in the central nervous system. The aim of this study was to determine the antidepressant effect of GGA in a chronic mild stress (CMS) model of depression. We confirmed that CMS in rats caused a reduction in locomotor activity and an increase in the levels of monoamine oxidase-A (MAO-A) and caspase-3 in the hippocampus. GGA treatment reversed stress-induced alterations in locomotor activity and target levels of MAO-A and caspase-3. In addition, GGA treatment induced heat shock protein 70 (Hsp70) expression in the hippocampus. These findings suggest that GGA possesses an antidepressant activity in a CMS model of depression. The activity of GGA in the relief of depression may be mediated via the induction of Hsp70 expression to suppress MAO-A expression and the apoptosis cascade.